X-box-binding protein 1 is required for pancreatic development in Xenopus laevis

摘要

X-box-binding protein 1(XBP1)is a protein containing the basic leucine zipper structure.It belongs to the cAMP-response element binding protein(CREB)/activating transcription factor transcrip-tion factor family.As the main transcription factor,spliced XBP1(XBP1s)participates in many physiological and pathological processes and plays an important role in embryonic development.Previous studies showed that XBP1-knockout mice died because of pancreatic exocrine function deficiency,indicating that XBP1 plays an important role in pancreatic development.However,the exact role of XBP1 in pancreatic development remains unclear.This study aimed to investi-gate the role of XBP1 in the pancreatic development of Xenopus laevis embryos.Whole-mount in situ hybridization and quantitative real-time PCR results revealed that the expression levels of pancreatic progenitor marker genes pdx1,p48,ngn3,and sox9 were downregulated in XBP1s mor-pholino oligonucleotide(MO)-injected embryos.The expression levels of pancreatic exocrine and endocrine marker genes insulin and amylase were also downregulated.Through the overexpres-sion of XBP1s,the phenotype and gene expressions were opposite to those in XBP1s MO-injected embryos.Luciferase and chromatin immunoprecipitation assays showed that XBP1s could bind to the XBP1-binding site in the foxa2 promoter.These results revealed that XBP1 is required in the pancreatic development of Xenopus laevis and might function by regulating foxa2.